The MAC, Mouse Adenocarcinoma of the Colon series of transplantable tumours have been developed from primary tumours induced by dimethylhydrazine. They are valuable as secondary screening models, and have a range of sensitivities to 5-fluorouracil FU treatment. The object of the current study is to use this model system to try to identify the reasons why only about one fifth of patients with colorectal cancer respond to FU, and to explore how such knowledge might predict the sensitivity of human tumours prior to therapy. The MAC tumours are in general poorly responsive to the standard chemotherapeutic agents and show a range of responses to FU, analogous to that found in human tumours. The levels of a number of enzymes known to be involved in FU metabolism are being measured along with the intrinsic levels of the nucleoside and nucleotide pools that could counteract the effects of FU metabolites in the DNA synthetic pathway. An attempt is being made to correlate the various parameters with sensitivity to FU, and to try to develop a system that is based on a biopsy specimen would yield a biochemical "fingerprint" that could be used clinically as a "predictive test" for responsiveness to FU. BIBLIOGRAPHIC REFERENCES: J.A. Double, E.H. Cooper and J.C. Goligher (1977). Hydrolytic Enzymes in Colorectal Cancer. Biomedicine, 27, 11-13. J.A. Double and E.H. Cooper (1977). Development of Model Colorectal Cancer Systems for Pharmacological Research. In: "Digestive Tract Cancer" ed. M. Lipkin, Plenum Press, New York (in press).